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Plasmodium falciparum Gametocyte Culture and Mosquito Infection Through Artificial Membrane Feeding
Published on: July 3, 2020
Parasite infectivity and immunity to Plasmodium falciparum gametocytes in Gambian children
C J Drakeley1, W Eling, K Teelen
1Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel St., London WC1E 7HT, UK. chris.drakeley@lshtm.ac.uk
Insights
Immunity against malaria
Area of Science:
- Immunology
- Infectious Diseases
- Vaccinology
Background:
- Natural Plasmodium falciparum infections can induce immunity to sexual stages.
- Understanding this immunity is crucial for developing transmission-blocking vaccines (TBVs).
- Gametocyte carriers in endemic areas are key reservoirs for malaria transmission.
Purpose of the Study:
- To assess functional transmission-blocking immunity in Gambian children.
- To identify serological correlates of this immunity.
- To evaluate antibody responses against key Plasmodium falciparum sexual stage antigens.
Main Methods:
- Standard membrane-feeding assays (SMFA) and direct membrane-feeding assays (DMFA) were used.
- Serological assays measured IgG1 responses to whole parasites, live gametes, Pfs230, and Pfs48/45.
- Correlation analyses were performed between serological data and transmission-blocking activity.
Main Results:
- 14/55 sera showed transmission-blocking activity in SMFA, correlated with IgG1 to Pfs48/45.
- Direct membrane-feeding assays with autologous isolates showed activity in 4/29 sera.
- No correlation was found between SMFA and DMFA results or between DMFA and serological assays.
Conclusions:
- Functional transmission-blocking immunity exists in young Gambian children.
- Antibodies to Pfs48/45 are associated with transmission-blocking activity in laboratory assays.
- Discrepancies between assays suggest antigen variation or alternative immunity mechanisms, impacting TBV design.
Abstract:
Immunity to the sexual stages of Plasmodium falciparum can be induced during natural infections. Characterization of this immunity may facilitate the design of a transmission-blocking vaccine (TBV). This study aimed to assess the prevalence and serological correlates of functional transmission-blocking immunity in Gambian children (aged 1-4 years old) who were P. falciparum gametocyte carriers. Serological assays showed 100% response to fixed, whole parasites but only 42% to live gametes. Responses to the antigens Pfs230 and Pfs48/45 were 54.1% and 37.3%, respectively, in an IgG1 ELISA. 14/55 sera were capable of reducing the infectivity of laboratory isolate NF54 in a standard membrane-feeding assay (SMFA). This activity was strongly correlated with IgG1 responses to Pfs48/45 (r = 0.49, P < 0.001) and to a serological reaction with epitopes of the same molecule (r = 0.38, P = 0.003). A weaker correlation was observed with IgG1 to Pfs230 (r = 0.29, P = 0.03). In direct membrane feeding assays (DMFA) with autologous isolates, sera from 4/29 children showed transmission-blocking activity. There was no correlation with serological assays and the DMFA or between the SMFA and DMFA. This may be caused by variation in sexual stage antigens and/or alternative modes of transmission-blocking immunity, both of which have implications for vaccine implementation.
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